Over the past 2 decades, prescription drug emergencies and fatalities have reached an epidemic level. A confluence of medical, regulatory, economic, and pharmaceutical industry–driven factors contributed to the expansion of opioid treatment for nonmalignant pain, which parallels the increase of nonmedical use and opioid addiction. Opioid-based treatments were proved beneficial for acute and cancer pain, and health care providers were encouraged to apply these same principles to the treatment of chronic nonmalignant pain. However, chronic pain often has complex causes exacerbated by comorbid psychiatric conditions and stressful life events. The unfortunate lessons learned from the effort to improve pain treatment are that the potential for misuse and addiction with long-term opioid exposure is elevated in vulnerable individuals.